MPB residues 90-101 are encephalitogenic in SJL mice (H-2s), while residues 1-9 are encephalitogenic in PL mice (H 2u). Utilizing SJL x PL (Fl) mice the relationship between encephalitogenicity and gentic background were previously examined. It was found that the encephalitogenicity of antigen was dependent upon I-A haplotype of antigen presenting cell. T-cells from Fl mice immunized with MBP fragment 1-37 (containing 19 fragment) were positively selected on PL (I-Au) parental macrophages. These cells transferred disease to 100% recipient naive Fl mice. Examination of spleen cell populations during the course of disease in the mice revealed the presence of T-cells responsive to 1-37, as well as other MBP factions (i.e. 89-169). In addition to I-Au restricted responses, I-As-restricted responses were also observed. These findings demonstrated that T-cells with novel epitope specificities and class 11 MHC restriction requirements were generated during the course of disease. Such cells may be involved in the pathogenesis of chronic disease (i.e., initiation of relapses). Significant progress on this project was not possible due to the inability to obtain sufficient Fl mice. These mice are solely distributed by Jackson Labs which suffered a debilitating fire resulting in loss of many breeder pairs including the Fl mouse stock. Attempts to breed our own were successful, but resulted in only a limited number of mice available for research. The supply at Jackson has been reestablished and we are currently performing experiments with these mice.